Comparison of <sup>18</sup>F-FDG and PiB PET in Cognitive Impairment

Lowe, Val J.; Kemp, Bradley J.; Jack, Clifford R.; Senjem, Matthew L.; Weigand, Stephen D.; Shiung, Maria M.; Smith, Glenn E.; Knopman, David S.; Boeve, Bradley F.; Mullan, Brian P.; Petersen, Ronald C.

doi:10.2967/jnumed.108.058529

Cited by 182 publications

(152 citation statements)

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“…Importantly, Ab deposition in 11 C-PIB-positive AD patients was greatest in characteristic neocortical regions not including the MTL, which is consistent with published histopathologic (3) and imaging data (6,29). The mechanism by which neocortical amyloid deposition leads to remote dysfunction of hippocampal archicortex and adjacent MTL neocortex is currently under debate.…”

Section: Discussionsupporting

confidence: 73%

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

et al. 2013

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Amyloid-b (Ab) deposition is a pathologic hallmark of Alzheimer disease (AD). Although the typical spatial distribution pattern of Ab deposition in early AD mainly involves regions distant from the hippocampus, the predominant clinical feature is impairment of hippocampusdependent memory. We aimed at elucidating the relationship between neocortical Ab load, regional neuronal function, and memory impairment. Methods: Thirty patients with early AD underwent combined 11 C-Pittsburgh compound B ( 11 C-PIB) and 18 F-FDG PET and memory assessments. Composite measures of hemispheric Ab load were calculated by volume-weighted mean values of neocortical 11 C-PIB binding. Voxelwise 18 F-FDG uptake was used as a measure of regional glucose metabolism reflecting neuronal activity. We investigated the relationship between left-and right-hemispheric Ab load and regional glucose metabolism (voxelwise analyses). In addition, we assessed the correlations of hemispheric Ab load (region-ofinterest-based analyses) and regional glucose metabolism (voxelwise analysis) with memory performance. Analyses were corrected for age and sex. Results: Higher Ab load in the left hemisphere was associated with reduced glucose metabolism of the left medial temporal lobe (MTL; r 2 5 0.38) and correlated with worse wordlist recall (r 5 20.37; partial correlation controlled for sex and age). Furthermore, wordlist recall correlated with regional glucose metabolism in the bilateral MTL and precuneus-posterior cingulate cortex and right lingual gyrus (r 2 5 0.24). Conclusion: We demonstrated an association between the left-hemispheric Ab load and impairment of the left MTL in AD at 2 different levels: regional hypometabolism and verbal memory. This correlation suggests that neocortical amyloid deposition is connected to or even drives neuronal dysfunction and neurodegeneration of the MTL, which is associated with impaired episodic memory processing as a clinical core symptom of AD.Key Words: Alzheimer's disease; episodic memory; positron emission tomography; Pittsburgh compound B; amyloid J Nucl Med 2013; 54:1909 54: -1914 54: DOI: 10.2967 Theamyl oid cascade hypothesis of Alzheimer disease (AD) posits that cortical amyloid-b (Ab) deposition is related to downstream neuronal dysfunction and cognitive impairment (1). Ab plaques presumably do not directly impair cognition but rather promote tau pathology in distant vulnerable neurons, which in turn leads to cognitive deficits (2). Intriguingly and at present not fully understood, the spatial distribution of Ab deposition in early AD mainly involves regions that are distant from the hippocampus, although the predominant clinical feature is impairment of hippocampus-dependent memory (3). With the advent of Ab PET imaging, most commonly using the radiotracer 11 C-Pittsburgh compound B ( 11 C-PIB (4)), quantitative in vivo assessment of the Ab load in the human brain has become feasible. Furthermore, PET imaging of regional cerebral glucose metabolism with 18 F-FDG represents an established marker of neuro...

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Section: Discussionsupporting

confidence: 73%

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

et al. 2013

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“…Cerebellar uptake was used as an internal reference region of interest for PiB-PET uptake normalization. The global PiB retention standard uptake value ratio (SUVR) was obtained from the bilateral parietal (including posterior cingulate and precuneus), temporal, prefrontal, orbitofrontal, and anterior cingulate regions as previously described (Jack et al, 2008;Lowe et al, 2009). …”

Section: C-pittsburgh Compound B-pet Image Analysismentioning

confidence: 99%

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Sarro¹,

Senjem

Lundt

et al. 2016

Brain

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Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-b deposition as measured with 11 C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-b deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-b deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline 11 C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent 11 C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on threedimensional T 1 -weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline 11 C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline 11 C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P 5 0.05). Greater baseline 11 C-Pittsburgh compound B standard unit value ratio was also associated with greater ventricular expansion rates (P 5 0.01) and greater worsening over time in Clinical Dementia Rating Scale, sum of boxes (P = 0.02). In conclusion, in patients with probable dementia with Lewy bodies, higher amyloid-b deposition at baseline is predictive of faster neurodegeneration in the cortex and also in the striatum. This distribution is suggestive of possible interactions among amyloid-b, tau and a-synuclein aggregates, which needs further investigation. Furthermore, higher amyloid-b deposition at baseline predicts a faster clinical decline over time in patients with probable dementia with Lewy bodies. Keywords: DLB; structural MRI; beta-amyloid; amyloid imaging; brain atrophy Abbreviations: AChEI = acetylcholinesterase inhibitor; CDR-SOB = Clinical Dementia Rating scale, Sum of Boxes; DLB = dementia with Lewy bodies; MMSE = Mini-Mental State Examination; PiB = 11 C-Pittsburgh compound B; SUVR = standardized uptake value ratio; TBM-SyN = tensor-based morphometry using symmetric diffeomorphic image normalization; UPDRS-III =

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“…18 A normalized FDG uptake value was calculated for each ROI in reference to the pons: raw average ROI/raw average reference ROI. A standard FDG uptake value (SUV) was also calculated for each ROI including the pons: (raw average ROI/[injected dose/weight, kg]).…”

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confidence: 99%

Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers

et al. 2013

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Objective: In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [18 F]-fluorodeoxyglucose (FDG)-PET in progranulin (GRN) mutation carriers prior to frontotemporal dementia (FTD) onset.Methods: Nine mutation carriers (age 51.5 6 13.5 years) and 11 noncarriers (age 52.7 6 9.5 years) from 5 families with FTD due to GRN mutations underwent brain scanning with FDG-PET and MRI and clinical evaluation. Normalized FDG uptake values were calculated with reference to the pons. PET images were analyzed with regions of interest (ROI) and statistical parametric mapping (SPM) approaches.Results: Compared with noncarriers, GRN mutation carriers had a lowered anterior-to-posterior (AP) ratio of FDG uptake (0.86 6 0.09 vs 0.92 6 0.05) and less left-right asymmetry, consistent with an overall pattern of right anterior cerebral hypometabolism. This pattern was observed regardless of whether they were deemed clinically symptomatic no dementia or asymptomatic. Individual ROIs with lowered FDG uptake included right anterior cingulate, insula, and gyrus rectus. SPM analysis supported and extended these findings, demonstrating abnormalities in the right and left medial frontal regions, right insular cortex, right precentral and middle frontal gyri, and right cerebellum. Right AP ratio was correlated with cognitive and clinical scores (modified Mini-Mental State Examination r 5 0.74; Functional Rating Scale r 5 20.73) but not age and years to estimated onset in mutation carriers. Conclusion:The frontotemporal lobar degenerative process associated with GRN mutations appears to begin many years prior to the average age at FTD onset (late 50s-early 60s). Right medial and ventral frontal cortex and insula may be affected in this process but the specific regional patterns associated with specific clinical variants remain to be elucidated. The multifaceted clinical syndrome of frontotemporal dementia (FTD) arises from degeneration of the frontal and temporal lobes (frontotemporal lobar degeneration). Mutations in the gene encoding progranulin (GRN), discovered in 2006, 1,2 are found in 5%-20% of those with familial FTD (FTD-GRN).2,3 Despite the common haploinsufficiency mechanism 1 and transactive response DNA-binding protein M r 43 kD (TDP-43) neuropathology, 4 there is phenotypic variation in FTD-GRN, with behavioral variant FTD (bvFTD), progressive nonfluent aphasia (PNFA), and corticobasal syndrome.5 Mean age at onset is 59-65 years, but can range from 35 to 87 years. 6 In GRN mutation carriers with FTD, an asymmetric pattern of brain structural abnormalities is found, with severe gray matter loss involving frontal, anterior temporal, but also posterior temporal and inferior parietal regions. [7][8][9] There is only very limited evidence on brain

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Comparison of ¹⁸F-FDG and PiB PET in Cognitive Impairment

Cited by 182 publications

References 40 publications

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers

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Comparison of 18F-FDG and PiB PET in Cognitive Impairment

Cited by 182 publications

References 40 publications

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers

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Comparison of ¹⁸F-FDG and PiB PET in Cognitive Impairment